Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 26, 2015
Previous Article Next Article

Synthesis and biological evaluation of non-glucose glycoconjugated N-hydroyxindole class LDH inhibitors as anticancer agents

Author affiliations

Abstract

Inhibitors of human lactate dehydrogenase A (LDH-A) are promising therapeutic agents against cancer. The development of LDH-A inhibitors that possess cellular activities has so far proved to be particularly challenging, since the enzyme's active site is narrow and highly polar. In the recent past, we were able to develop a glucose-conjugated N-hydroxyindole-based LDH-A inhibitor designed to exploit the sugar avidity expressed by cancer cells (the Warburg effect). Herein we describe a structural modulation of the sugar moiety of this class of inhibitors, with the insertion of α-D-mannose, β-D-gulose, or β-N-acetyl-D-glucosamine portions in their structures. Their stereospecific chemical synthesis, which involves a substrate-dependent stereospecific glycosylation step, and their biological activity in reducing lactate production and proliferation in cancer cells are reported. Interestingly, the α-D-mannose conjugate displayed the best properties in the cellular assays, demonstrating an efficient antiglycolytic and antiproliferative activity in cancer cells.

Graphical abstract: Synthesis and biological evaluation of non-glucose glycoconjugated N-hydroyxindole class LDH inhibitors as anticancer agents

Back to tab navigation

Supplementary files

Article information


Submitted
16 Jan 2015
Accepted
10 Feb 2015
First published
11 Feb 2015

RSC Adv., 2015,5, 19944-19954
Article type
Paper
Author version available

Synthesis and biological evaluation of non-glucose glycoconjugated N-hydroyxindole class LDH inhibitors as anticancer agents

V. Di Bussolo, E. C. Calvaresi, C. Granchi, L. Del Bino, I. Frau, M. C. Dasso Lang, T. Tuccinardi, M. Macchia, A. Martinelli, P. J. Hergenrother and F. Minutolo, RSC Adv., 2015, 5, 19944
DOI: 10.1039/C5RA00946D

Social activity

Search articles by author

Spotlight

Advertisements